Thrombospondin binding to specific sequences within the A alpha- and B beta-chains of fibrinogen.
Thrombospondin is a multifunctional adhesive glycoprotein which binds to the surface of resting and activated platelets. Thrombospondin also binds to a variety of proteins, including fibrinogen. The interactions between platelet-bound thrombospondin and fibrinogen are thought to facilitate irreversible platelet aggregation. Both the A alpha- and B beta-chains of fibrinogen specifically bind to thrombospondin. Cyanogen bromide cleavage products of the fibrinogen A alpha- and B beta-chains, and synthetic peptides corresponding to specific regions of these cleavage products were utilized to identify the regions of the fibrinogen A alpha- and B beta-chains which bind to thrombospondin. Cyanogen bromide fragments of the A alpha- and B beta-fibrinogen chains, resolved by gel filtration and reversed-phase chromatography, were examined for thrombospondin binding activity. Thrombospondin specifically bound to the A alpha-chain fragment encompassing residues 92-147 and the B beta-chain fragment encompassing residues 243-305. Analyses of the binding characteristics of two series of overlapping synthetic peptides revealed that peptides corresponding to residues 113-126 of the A alpha-chain and residues 243-252 of the B beta-chain retained thrombospondin binding activity. Separate bovine serum albumin conjugates of the active A alpha-chain and B beta-chain peptides inhibited platelet aggregation. These studies reveal that fibrinogen possesses at least two unique sequences which are recognized by thrombospondin and that such interaction may affect platelet aggregation.
Bacon-Baguley
T
T
Department of Physiology, Wayne State University, Detroit, Michigan 48201.
Ogilvie
M L
ML
Gartner
T K
TK
Walz
D A
DA
D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003488:Cyanogen Bromide; D005340:Fibrinogen / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010446:Peptide Fragments / Q000302:isolation & purification; D010974:Platelet Aggregation; D011485:Protein Binding; D019699:Thrombospondins
D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D010446:Peptide Fragments; D019699:Thrombospondins; D005340:Fibrinogen; D003488:Cyanogen Bromide